Pulmonary Tuberculosis: Epidemiology And Diagnostic Methods

Pulmonary tuberculosis is the leading cause of morbidity and mortality, with approximately a third of the world’s population latently infected. This poses a serious health threat because about 10% of the infected individuals develop active disease. Pulmonary tuberculosis refers to any bacteriologically confirmed or clinically diagnosed case of TB involving the lung parenchyma or the tracheobronchial tree. Pulmonary tuberculosis results from infection of the lungs with Mycobacterium tuberculosis. This is due inhalation of aerosols containing M. tuberculosis bacilli from another infected person.

Primary infection leads to clinical disease in only 10% of the individuals, and the remaining individuals are able to mount a strong immune response that arrests further growth of the M. tuberculosis hence become latent. Latently infected individuals can reactivate to disease under certain conditions such as HIV/AIDS, transplantation with immunosuppressant use, silicosis, close contact with a PTB patient, tumor necrosis factor-alpha, chronic renal failure and hemo-dialysis. There is 5%–15% risk of developing active disease every year and lifetime risk of approximately 50% in HIV coinfected individuals. Active tuberculosis disease is characterized fever, weight loss and night sweats among others.

Epidemiology of pulmonary tuberculosis

Tuberculosis now ranks as the leading cause of death from an infectious disease. In 2015, there were 10. 4 million new TB cases worldwide of which 62% and 90% were males and adults respectively. Of the incident cases observed worldwide in 2015, 11% were in HIV positive individuals. Moreover, there was an estimated 1. 4 million TB deaths in HIV negative individuals and an extra 0. 4 million deaths in HIV positive individuals in 2015. The case fatality rate of tuberculosis worldwide was 17% in 2015. In 2015, the incident rate of TB varied among countries and ranged between 10 per 100, 000 population in high-income countries and 300 per 100, 000 population in high TB burden countries as shown in Fig one below. The African region has the highest TB/HIV burden and particularly Sub Saharan Africa has over 50% of the TB cases coinfected with HIV. Uganda is one of the high TB/HIV burden countries in the world with an estimated incidence of 79 cases per 1000 persons and mortality rate of 14 deaths per 100, 000 persons as per 2015.

A study carried out in Nigeria in 2015 that reviewed documents of TB cases from January 2005 to April 2015 revealed a prevalence of 25%. Moreover another study performed in 2015 in Uganda to assess the epidemiology of TB in children in Kampala district demonstrated that the percentage of pulmonary TB cases 89%.

Major diagnostic methods for Pulmonary TB

Radiologic examination

Chest X-ray is the main radiologic test perfomed on suspected TB patients and is very important in TB diagnosis. However, the range of radiologic manifestation depends on the level of HIV- immunodeficiency and therefore chest radiography is rarely beneficial these individuals. Moreover it is difficult to radiologically distinguish between active and inactive tuberculosis and other infections in HIV positive patients may lead to atypical appearance.

Microscopy

Detection of acid- fast bacteria in sputum through microscopic examination is the most frequent method for TB detection. Light microscopy is simple, cheap, and quick to perform however for a sample to be considered smear positive, it must contain about 105 Mycobacteria per milliter. Its sensitivity is much lower in HIV co-infected individuals ranging between 43% to 51%. A study carried out in Rwanda in 2016 evaluated the diagnostic performance of genexpert showed that sensitivity was lower in HIV positive individuals (39%) as compared to HIV negative individuals (56%). Fluorescence microscopy is more sensitive than the light microscope, however, it is expensive and requires considerable technical expertise. Other alternatives including light emiting diode bulbs were evaluated and are currently being scaled up for TB diagnosis. Nonetheless, because the primary mode of TB detection in resource constrained areas is smear microscopy, a number of smear negative individuals go undetected leading to delay in intiation of therapy.

Culture

M. tuberculosis isolation by culture from sputum of suspected individuals is the gold standard and has been recommended to assist in TB diagnosis in HIV co-infected individuals. The major advantage of culture is the fact that it is more sensitive because fewer bacilli can be detected and it also enables species identification and drug susceptibility testing. However, traditional culture methods are complex, require trained laboratory technicians and are time-consuming requiring 2-6 weeks which would result in the delay of initiation of therapy.

To overcome some of these problems, newer modifications that are more rapid have been created including the liquid culture. Liquid culture is a more rapid culture method that is able detect growth of Mycobacteria within 1-2 weeks by Oxygen sensors, increasing the case yield by 10% over solid media. Howeverliquid culture is very prone to contamination and as a result, approximately 5% to 10% fail to yield results. Moreover it is also very expensive and its requirement for safe disposal of the radioactive waste precludes its use in peripheral laboratories. An example is the automated liquid culture system is the BACTEC MGIT 960 based on modified Middlebrook 7H9 Broth with an oxygen-sensitive fluorescent detection technology.

A study conducted in UK in 2017 assessed the performance of Xpert MTB/RIF in detecting smear negative tuberculosis showed an overall sensitivity of 84% and specificity of 99%.

Nucleic-acid amplification tests

Nucleic Acid Amplification techniques have a short turnaround time of about 3-6 hours and can be performed on the stored samples. The most common nucleic acid amplification technique is polymerase chain reaction (PCR) technique which depends on amplification of specific nucleic acids regions the M. tuberculosis complex. GeneXpert MTB/RIF is a real time PCR- based molecular assay that amplifies a specific sequence of rpoB gene in M tuberculosis and detects RIF resistance mutations as a marker for multi-drug resistance tuberculosis. It is less time consuming as compared to culture and provides results in less than 2 hours. However it is unable to monitor treatment progress and to detect resistance to other drugs other than rifampicin. Moreover it requires constant electric power supply, need of appropriate staff training, cartridge supply and storage conditions and this limits its use in resource limited settings such as rural environments.

A study carried in Uganda in 2017 to evaluate the effect of sputum quality on the performance of GeneXpert on suspected TB patients revealed that the overall sensitivity and specificity of GeneXpert was 53% and 95% respectivity.

Immunological tests

These include the tuberculin skin test (TST) and interferon gamma release assay (IGRA). However, these tests have limited diagnostic potential as they cannot distinguish between latent infection, active pulmonary TB. Moreover negative results cannot entirely exclude presence of disease. TST is limited by BCG vaccination cross reactivity to yield false positives. Other factors causing immunosuppression including HIV, malnutitution, etc. reduce the response of the TST yielding false negatives. The diagnostic potential of IGRA for the diagnosis of PTB on various body fluid has been investigated by various studies. A study conducted in Uganda in 2010 investigated the role of IGRAs in diagnosis of PTB in patients with advanced HIV infection revealed that the sensitivity of IGRAs was 73% and specificity of 54%.